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在一组退伍军人样本中,血清素转运体的“S”等位基因与重度抑郁症无关。

The "S" Allele of the Serotonin Transporter Is Not Associated with Major Depression in a Sample OF Veterans.

作者信息

Cornelius Jack R, Haas Gretchen L, Goldstein Gerald, Hanusa Barbara, Walker Jon D, Fox Lauren J, Ferrell James

出版信息

Adv Genet Res. 2014;12:1-10.

Abstract

The results of some studies suggest that the serotonin transporter-linked polymorphic region (5-HTTLPR) short (S) allele, relative to the long (L) allele, is associated with risk for Major Depressive Disorder (MDD), and thus serves as a biomarker for MDD, while results from other studies do not support that conclusion. Persons with an S allele demonstrate a 2- to 2.5 fold decrease in serotonin transcription rate compared to the L-allele, which may increase their risk for MDD. Differences in study populations may help explain the differences in findings between those meta-analyses. To date, there have been no published reports which have addressed the possible association between the S allele and MDD among military veterans. This manuscript describes a first study to assess the possible association of the S allele with MDD among a study population of veterans in treatment for a substance use disorder. We hypothesized that the S allele would be associated with MDD in our study sample. Subjects signing informed consent were 101 Veterans recruited from VA behavioral health and substance use treatment clinics in the VA Pittsburgh Healthcare System, and 91 of those subjects were genotyped for 5-HTTLPR polymorphisms. The study sample from whom genetic material was collected included 82 males and 9 females, of whom 53 were white, 38 were black, and one was "other". Fifty-four members of the study sample (59%) met DSM-IV criteria for an MDD on the SCID. Forty-five of the subjects demonstrated one or two S alleles, while 46 did not do so. The presence of the S allele of the serotonin transporter was not found to be significantly associated with the diagnosis of major depressive disorder in our sample (Chi-square=0.1.63, df=1, p=0.199). That finding, in combination with other recent negative findings from other researchers involving non-veterans, raises questions regarding the clinical utility of utilizing genetics tests involving the assessment of the alleles of the serotonin transporter as a possible biomarker for MDD.

摘要

一些研究结果表明,相对于长(L)等位基因,血清素转运体相关多态性区域(5-HTTLPR)的短(S)等位基因与重度抑郁症(MDD)风险相关,因此可作为MDD的生物标志物,而其他研究结果并不支持这一结论。与L等位基因相比,携带S等位基因的人血清素转录率降低2至2.5倍,这可能会增加他们患MDD的风险。研究人群的差异可能有助于解释这些荟萃分析结果之间的差异。迄今为止,尚无已发表的报告探讨退伍军人中S等位基因与MDD之间的可能关联。本手稿描述了第一项研究,旨在评估在患有物质使用障碍的退伍军人研究人群中,S等位基因与MDD之间的可能关联。我们假设在我们的研究样本中,S等位基因与MDD相关。签署知情同意书的受试者为从匹兹堡退伍军人医疗系统的退伍军人事务部行为健康和物质使用治疗诊所招募的101名退伍军人,其中91名受试者进行了5-HTTLPR多态性基因分型。收集了遗传物质的研究样本包括82名男性和9名女性,其中53名是白人,38名是黑人,1名是“其他”。研究样本中的54名成员(59%)符合DSM-IV中关于SCID上MDD的标准。45名受试者显示有一个或两个S等位基因,而46名受试者没有。在我们的样本中,未发现血清素转运体S等位基因的存在与重度抑郁症的诊断有显著关联(卡方=0.163,自由度=1,p=0.199)。这一发现,连同其他研究人员近期对非退伍军人的其他负面研究结果,引发了关于将涉及血清素转运体等位基因评估的基因检测作为MDD可能生物标志物的临床效用的质疑。

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